Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression.

Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation.

The Duration of Neonatal Phototherapy and Allergic Disorders: The Japan Environment and Children's Study.

INTRODUCTION: Currently, the association between the duration of neonatal phototherapy and the risk of allergic disorders has not been reported. This observational cohort study aimed to examine the association between allergic disorders, including food allergies, that are present before 3 years of age and the duration of phototherapy using the nationwide birth cohort data. METHODS: The Japan Environment and Children's Study was a nationwide birth cohort study. Data of 77,064 infants aged 1 year, 1.5 years, 2 years, and 3 years were analyzed. We divided the participants into three groups: no phototherapy, short phototherapy (1-24 h), and long phototherapy (>24 h) and evaluated the cumulative incidence of allergic disorders before 3 years of age, including asthma, atopic dermatitis, and food allergies. Logistic regression analysis was performed to assess the impact of phototherapy duration on the cumulative incidence of allergic disorders. RESULTS: After adjustment for potential risk factors, long phototherapy was found to be positively associated with food allergies at age 2 years (OR: 1.16; 95% CI: 1.01-1.33) and all allergic disorders at age 3 years (OR: 1.12; 95% CI: 1.01-1.24), including food allergies (OR 1.18; 95% CI: 1.04-1.35). CONCLUSION: A long duration of neonatal phototherapy was positively associated with the risk of allergic disorders, especially food allergies.

Association between neonatal phototherapy and sleep: The Japan Environment and Children's Study.

This observational cohort study aimed to evaluate the association between the duration of neonatal phototherapy and sleep-and-wakefulness states at 1 month, 1.5 years, and 3 years of age. We analysed data from 77,876 infants using the Japan Environment and Children's Study, a nationwide birth cohort study. The participants were divided into three groups: no phototherapy, short phototherapy (1-24 h), and long phototherapy (>24 h). Multiple regression analysis was performed to assess the effect of phototherapy duration on infant sleep at each age after adjusting for potential risk factors. A longer duration of phototherapy was associated with a shorter sleep time over 24 h at 1 month of age (ß, -0.62; SE, -0.77 to -0.47) when compared with a shorter duration of, or no, phototherapy, following the adjustment of confounding factors. Contrastingly, the short duration group, when compared with the no phototherapy group, was associated with later sleep onset (ß, 0.04; SE, 0.00-0.08) and later sleep offset (ß, 0.05; SE, 0.01-0.09) at 1.5 years of age. We concluded that the duration of phototherapy may be transiently associated with sleep duration in infants, as emphasised by the shortening of the total sleep time per 24 h at 1 month of age.

Association Between Mode of Delivery and Postpartum Depression: The Japan Environment and Children's Study (JECS).

BACKGROUND: Postpartum depression (PPD) has been associated with adverse health outcomes, including maternal suicide. Mode of delivery has been suggested to be a risk factor for PPD, but no large cohort study has examined the association between mode of delivery and PPD. We aimed to examine the association between mode of delivery and risks of PPD at 1 and 6 months after childbirth. METHODS: In a nationwide study of 89,954 mothers with a live singleton birth, we examined the association between mode of delivery and risks of PPD. PPD was evaluated using the Edinburgh Postnatal Depression Scale (≥13) at 1 and 6 months after childbirth. Odds ratios (ORs) with 95% confidence intervals (CIs) of PPD were calculated using multivariable logistic regression analyses after adjustment of antenatal physical, socioeconomic, and mental factors. RESULTS: Among 89,954 women, 3.7% and 2.8% had PPD at 1 and 6 months after childbirth, respectively. Compared with unassisted vaginal delivery, cesarean section (CS) was marginally associated with PPD at 1 month but not at 6 months; adjusted ORs were 1.10 (95% CI, 1.00-1.21) and 1.01 (95% CI, 0.90-1.13), respectively. The association with PPD at 1 month was evident in women with antenatal psychological distress (adjusted OR 1.15; 95% CI, 1.03-1.28). The observed associations were attenuated after adjusting for infant feeding method. CONCLUSION: Women who had antenatal psychological distress and underwent CS delivery may be regarded as a target for monitoring PPD.

Association Between Interpregnancy Interval and Risk of Preterm Birth and Its Modification by Folate Intake: The Japan Environment and Children's Study.

BACKGROUND: Both short and long interpregnancy intervals (IPIs) have been associated with risk of preterm birth, but the evidence is limited in Asians. It is also uncertain whether the association is modified by dietary folate intake or folic acid supplementation during pregnancy. Thus, we examined associations between IPI and risk of preterm birth and effect modification of those associations by dietary intake of folate and supplementation with folic acid on the basis of a nationwide birth cohort study. METHODS: Among 103,062 pregnancies registered in the Japan Environment and Children's Study, 55,203 singleton live-birth pregnancies were included in the analysis. We calculated IPI using birth date, gestational age at birth of offspring, and birth data of the latest offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) of the risk of preterm birth were estimated according to IPI categories. RESULTS: Both <6-month and ≥120-month IPIs were associated with an increased risk of preterm birth, compared with an 18-23-month IPI. The multivariable ORs were 1.63 (95% CI, 1.30-2.04) for <6-month and 1.41 (95% CI, 1.11-1.79) for ≥120-month IPIs. These associations were confined to women with inadequate intake of dietary folate and folic acid supplementation during pregnancy. Multivariable ORs were 1.76 (95% CI, 1.35-2.29) for <6-month IPI and 1.65 (95% CI, 1.24-2.19) for ≥120-month IPI. CONCLUSION: Both <6-month and ≥120-month IPIs were associated with an increased risk of preterm birth. These higher risks were confined to women with inadequate intake of dietary folate and folic acid supplementation during pregnancy.

Phototherapy and risk of developmental delay: the Japan Environment and Children's Study.

This observational cohort study aimed to examine the association between the duration of phototherapy for neonatal jaundice and the risk of developmental delay at 3 years of age using nationwide birth cohort data. Data from 76,897 infants were analyzed. We divided participants into four groups: no phototherapy, short phototherapy (1-24 h), long phototherapy (25-48 h), and very long phototherapy (> 48 h). The Japanese version of the Ages and Stages Questionnaire-3 was used to evaluate the risk of developmental delay at 3 years of age. Logistic regression analysis was performed to assess the impact of phototherapy duration on the prevalence of developmental delay. After adjustment for potential risk factors, a dose-response relationship was identified between the duration of phototherapy and Ages and Stages Questionnaire-3, and the differences were significant in four domains; odds ratio for communication delay was associated with short, long, and very long phototherapy = 1.10 (95% confidence interval 0.97-1.26), 1.32 (1.04-2.66), and 1.48 (1.11-1.98), respectively; for gross motor delay = 1.01 (0.89-1.15), 1.28 (1.03-2.58), and 1.26 (0.96-1.67); for problem solving delay = 1.13 (1.03-1.25), 1.19 (0.99-1.43), and 1.41 (1.11-1.79); and for personal social delay = 1.15 (0.99-1.32), 1.10 (0.84-1.44), and 1.84 (1.38-2.45). CONCLUSION: Longer duration of phototherapy is a predictive factor for developmental delay, making it important to avoid extended periods of phototherapy. However, whether it increases the prevalence of developmental delay remains unclear. WHAT IS KNOWN: • Phototherapy is a common treatment for neonatal jaundice, associated with both short-term and long-term complications. • However, an association between phototherapy and the prevalence of developmental delay has not been revealed in a large cohort study. WHAT IS NEW: • We identified that a long duration of phototherapy was a predictive factor for developmental delay at 3 years of age. • However, whether a long duration of phototherapy increases the prevalence of developmental delay remains unclear.

Self-reported eating habits and dyslipidemia in men aged 20-39 years: the Japan Environment and Children's Study.

BACKGROUND AND AIMS: Unhealthy eating behaviors, including eating fast, eating after satiety, skipping breakfast, and eating out are common among men aged 20-39 years. In this cross-sectional study, we aimed to examine the association between self-reported eating habits and the prevalence of dyslipidemia. METHODS: The participants of this study were 38,233 men aged 20-39 years, whose food consumption frequency related information was collected through a questionnaire. Dyslipidemia was defined as total cholesterol (TC) ≥190 mg/dL, fasting triglyceride (TG) ≥150 mg/dL and non-fasting TG ≥175 mg/dL, high-density lipoprotein cholesterol (HDL-C) <40 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥140 mg/dL. Odds ratios (ORs) and 95% confidence intervals were calculated relative to healthy eating habits using logistic regression, after adjustment for age, study unit, and other potential confounding factors. RESULTS: Moderate and fast speeds were associated with a higher prevalence of reduced HDL-C (by 27% and 26%, respectively) compared to slow speeds. Eating after satiety was associated with a higher prevalence of elevated TC (by 16%) and elevated TG (by 11%), elevated LDL-C (by 21%). Breakfast eating of 1-4 times/week and <1 time/week were associated with a higher prevalence of elevated TC (by 11% and 16%, respectively) and elevated LDL-C (by 21% and 38%, respectively) compared to that of ≥5 times/week. Eating out of ≥5 times/week was associated with a 13% higher prevalence of elevated TG. CONCLUSIONS: All of four unhealthy eating habits were associated with a higher prevalence of dyslipidemia in men aged 20-39 years.

The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke-Hennekam syndrome.

Menke-Hennekam syndrome-1 (MKHK1) is a congenital disorder caused by the heterozygous variants in exon 30 or 31 of CREBBP (CREB binding protein) gene mapped on 16p13.3. It is characterized by psychomotor delay, variable impairment of intellectual disability (ID), feeding difficulty, autistic behavior, hearing impairment, short stature, microcephaly, and facial dysmorphisms. The CREBBP loss-of-function variants cause Rubinstein-Taybi syndrome-1 (RSTS1). The function of CREBBP leading to MKHK1 has not been clarified so far, and the phenotype of MKHK1 significantly differs from that of RSTS1. We examined six patients with de novo pathogenic variants affecting the last exon of CREBBP, and they shared the clinical features of MKHK1. This study revealed that one frameshift and three nonsense variants of CREBBP cause MKHK1, and inferred that the nonsense variants of the last exon could further help in the elucidation of the etiology of MKHK1.

Long-term outcomes of children with neonatal transfer: the Japan Environment and Children's Study.

This study aimed to evaluate the association of neonatal transfer with the risk of neurodevelopmental outcomes at 3 years of age. Data were obtained from the Japan Environment and Children's Study. A general population of 103,060 pregnancies with 104,062 fetuses was enrolled in the study in 15 Regional Centers between January 2011 and March 2014. Live-born singletons at various gestational ages, including term infants, without congenital anomalies who were followed up until 3 years were included. Neurodevelopmental impairment was assessed using the Ages and Stages Questionnaire, third edition (ASQ-3) at 3 years of age. Logistic regression was used to estimate the adjusted risk and 95% confidence interval (CI) for newborns with neonatal transfer. Socioeconomic and perinatal factors were included as potential confounders in the analysis. Among 83,855 live-born singletons without congenital anomalies, 65,710 children were studied. Among them, 2780 (4.2%) were transferred in the neonatal period. After adjustment for potential confounders, the incidence of neurodevelopmental impairment (scores below the cut-off value of all 5 domains in the ASQ-3) was higher in children with neonatal transfer compared with those without neonatal transfer (communication: 6.5% vs 3.5%, OR 1.42, 95% CI 1.19-1.70; gross motor: 7.6% vs 4.0%, OR 1.26, 95% CI 1.07-1.49; fine motor: 11.3% vs 7.1%, OR 1.19, 95% CI 1.03-1.36; problem solving: 10.8% vs 6.8%, OR 1.29, 95% CI 1.12-1.48; and personal-social: 6.2% vs 2.9%, OR 1.52, 95% CI 1.26-1.83).   Conclusion: Neonatal transfer was associated with a higher risk of neurodevelopmental impairment at 3 years of age. What is Known: • Neonatal transfer after birth in preterm infants is associated with adverse short-term outcomes. • Long-term outcomes of outborn infants with neonatal transfer in the general population remain unclear. What is New: • This study suggests that neonatal transfer at birth is associated with an increased risk of neurodevelopmental impairment. • Efforts for referring high-risk pregnant women to higher level centers may reduce the incidence of neonatal transfer, leading to improved neurological outcomes in the general population.

Pregnancy outcomes after preterm premature rupture of membranes: The Japan Environment and Children's Study.

AIM: To evaluate the pregnancy outcomes of preterm premature rupture of membranes (preterm PROM; PPROM) by gestational age. METHODS: This cohort study analyzed data from the Japan Environment and Children's Study. Pregnancy outcomes were documented using descriptive statistics. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of complications. RESULTS: Data were collected for 104 062 fetuses, and 99 776 were eligible for inclusion. The incidences of early (18-23 weeks) and late (24-36 weeks) PPROM were 0.1% (n = 102) and 1.2% (n = 1205), respectively. Of the 1307 cases, 66 (5.0%) resulted in miscarriage or stillbirth. Overall, 85.6% (1119/1307) resulted in preterm births, and 9.3% (122/1307) in term births. There was a higher incidence of oligohydramnios (OR 6.82, 95% CI 4.07, 11.4; OR 2.42, 95% CI 1.72, 3.40), intrauterine infection (OR 11.9, 95% CI 7.06, 19.9; OR 4.39, 95% CI 3.01, 6.41), cesarean delivery (OR 3.31, 95% CI 2.32, 4.71; OR 1.34, 95% CI 0.97, 1.85), placental abruption (OR 5.57, 95% CI 2.30, 13.5; OR 5.40, 95% CI 3.58, 8.14), and 5-min Apgar score <7 (OR 35.3, 95% CI 21.5, 57.9; OR 2.66, 95% CI 1.75, 4.05) for early and late, compared to no, PPROM, respectively. Miscarriage or stillbirth was higher in early (OR 5.84, 95% CI 3.72, 9.15) and lower in late (OR 0.21, 95% CI 0.06, 0.68) compared to those without PPROM. CONCLUSIONS: This study described the epidemiology of pregnancy outcomes of early (occurring at the limit of viability) and late PPROM.

Clinical spectrum of individuals with de novo EBF3 variants or deletions.

Hypotonia, ataxia and delayed development syndrome (HADDS) (MIM#617330) is a neurodevelopmental disorder caused by heterozygous pathogenic variants in EBF3 (MIM; 607,407), which is located on chromosome 10q26, and was first reported in 2017. To date, missense, nonsense and frameshift variants have been reported as causes of HADDS, and EBF3 pathogenic variants have been predicted to result in nonsense-mediated mRNA decay and haploinsufficiency. It was also reported that total deletion of EBF3 associated with a 10q26.3 microdeletion also causes HADDS symptoms, supporting the concept that HADDS results from haploinsufficiency of EBF3. Here, we report eight unrelated individuals with heterozygous pathogenic variants of EBF3 or haploinsufficiency of EBF3 due to 10q26 deletion, who exhibit clinical findings including craniofacial features of HADDS. In a detailed examination of clinical manifestations in this study, revealed that neurogenic bladder was diagnosed in infancy (the median 6.5 months), was more frequent than previously reported, and required cystostomy in all but one case. For psychomotor delay, it was also found that their motor/skills values were significantly lower than their cognition/adaptation values (p = 0.0016; paired t-test). Therefore, that HADDS is a recognizable syndrome that shares its characteristic facial features, and that neurogenic bladder diagnosed in infancy and psychomotor delay with marked delay in motor/skills are noteworthy findings in the diagnosis and management of individuals with HADDS.

Blended phenotype of combination of HERC2 and AP3B2 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15.

Angelman syndrome is a neurodevelopmental disorder characterized by intellectual disability (ID), a distinctive gait pattern, abnormal behaviors, severe impairment in language development, and characteristic facial features. Most cases are caused by the absence of a maternal contribution to the imprinted region on chromosome 15q11-q13. Here, we present the first reported case of a 3-year-old boy with an atypical phenotype of Angelman syndrome due to uniparental isodisomy with two recessive homozygous pathogenic variants: in HERC2 and AP3B2. Known phenotypes related to HERC2 and AP3B2 include ID and early infantile epileptic encephalopathy, respectively. The patient had severe global developmental delay and profound ID and showed a happy demeanor, stereotypic laughter, and hand-flapping movements, but also irritability. Craniofacial dysmorphic features, including brachycephaly, strabismus, wide ala nasi, short philtrum, wide open mouth, and slight hypopigmentation were seen. Progressive microcephaly was noted. Magnetic resonance imaging of the brain showed delayed myelination and cerebral atrophy. Trio whole exome sequencing and CGH-SNP array analysis revealed paternal uniparental isodisomy of chromosome 15 and two coexisting recessive diseases resulting from homozygous HERC2 and AP3B2 pathogenic variants. The pathogenic variant in HERC2 was inherited from his heterozygous-carrier father, and the variant in AP3B2 was de novo. We suppose that these unusual features were the combination of the effect of three concomitant disorders.

Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children's Study.

BACKGROUND: Intervention studies have shown that isoflavone treatment improved glucose metabolism, indicating that soy intake may have a potential role in diabetes prevention. OBJECTIVES: We aimed to investigate the prospective association of soy isoflavone and soy food intakes with incidence of gestational diabetes mellitus (GDM) in a birth cohort study. METHODS: We recruited 97,454 pregnant women (median gestational age 12 weeks) between January 2011 and March 2014. Dietary intakes during the 12 months preceding study enrollment were assessed by a semi-quantitative food frequency questionnaire. The relative risks of GDM associated with soy isoflavone and soy food intakes were obtained by Poisson regression. Demographic information, histories of diseases, socioeconomic status, lifestyles, and dietary habits, obtained by a self-administrated questionnaire, were used for covariate adjustments. RESULTS: We identified 1904 cases of GDM (2.2%) among 84,948 women. Compared with those in the lowest quintile of soy isoflavone intake, women in the highest quintile were found to have experienced a significantly lower risk of GDM (multivariate relative risk = 0.82; 95% confidence interval: 0.70, 0.95; P for trend = 0.05). Similar results were observed for genistein and daidzein. Regarding soy foods, intakes of miso soup and natto were inversely associated with GDM incidence (both P for trend ≤ 0.01), whereas the association for tofu intake appeared to be nonlinear (P for trend = 0.74). CONCLUSIONS: Higher intakes of miso soup and natto before and during early pregnancy, compared with lower intakes, may be associated with a lower incidence of GDM.

Chocolate consumption and risk of gestational diabetes mellitus: the Japan Environment and Children's Study.

The association of chocolate consumption with risk of gestational diabetes has not been examined. We aimed to investigate the prospective association between chocolate consumption and risk of gestational diabetes in a large birth cohort in Japan. A total of 97 454 pregnant women with a median gestational age of 12 weeks were recruited from January 2011 to March 2014. Data on demographic information, disease history, socio-economic status, lifestyle and dietary habits were obtained at the study enrolment. Dietary intake during the past 12 months before study enrolment was assessed through a semi-quantitative FFQ. The logistic regression was used to obtain the OR of gestational diabetes in relation to chocolate consumption. Among 84 948 women eligible for the analysis, 1904 cases of gestational diabetes (2·2 %) were identified during the period of pregnancy. After controlling for potential confounding factors including age, smoking status, drinking status, education level, occupation, pre-pregnant BMI, depression, previous history of macrosomia babies, parity, physical activity and dietary factors, women in the highest quartile of chocolate consumption, compared with those in the lowest quartile, had a significantly lower risk of developing gestational diabetes (OR 0·78, 95 % CI 0·67, 0·90; P for trend = 0·002). Stratified analyses suggested that the association was not significantly modified by pre-pregnancy BMI, age, parity, smoking status or drinking status. The present prospective cohort study provided evidence that chocolate consumption was associated with a significant lower risk of gestational diabetes in Japanese women.

Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype.

RASopathies are phenotypically overlapping genetic disorders caused by dysregulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome, Costello syndrome, Neurofibromatosis type 1, Legius syndrome, Noonan syndrome with multiple lentigines, Noonan-like syndrome, hereditary gingival fibromatosis, and capillary malformation/arteriovenous malformation syndrome. Recently, six patients with craniosynostosis and Noonan syndrome involving KRAS mutations were described in a review, and a patient with craniosynostosis and Noonan syndrome involving a SHOC2 mutation has also been reported. Here, we describe patients with craniosynostosis and Noonan syndrome due to de novo mutations in PTPN11 and patients with craniosynostosis and CFC syndrome due to de novo mutations in BRAF or KRAS. All of these patients had cranial deformities in addition to the typical phenotypes of CFC syndrome and Noonan syndrome. In RASopathy, patients with cranial deformities, further assessments may be necessary to look for craniosynostosis. Future studies should attempt to elucidate the pathogenic mechanism responsible for craniosynostosis mediated by the RAS/MAPK signaling pathway.

Neurodevelopmental outcomes at age 3 years after moderate preterm, late preterm and early term birth: the Japan Environment and Children's Study.

OBJECTIVE: To assess the association between gestational age classification at birth and the risk of neurodevelopmental impairments at age 3 years. DESIGN: Cohort study using the Japan Environment and Children's Study database. PATIENTS: A total of 86 138 singleton children born without physical abnormalities at 32-41 weeks of gestation enrolled between January 2011 and March 2014. MAIN OUTCOME MEASURES: Neurodevelopmental impairment, evaluated using the Ages and Stages Questionnaire (third edition). METHODS: Logistic regression analysis was used to evaluate the risk of neurodevelopmental impairment in moderate preterm, late preterm and early term children compared with term children after adjusting for socioeconomic and perinatal factors. RESULTS: The respective adjusted ORs (95% CIs) of incidence of scores below the cut-off value (<-2.0 SD) at age 3 years for moderate preterm, late preterm and early term births, compared with full-term births, were as follows: communication, 2.40 (1.54 to 3.73), 1.43 (1.19 to 1.72) and 1.11 (1.01 to 1.21); gross motor, 2.55 (1.69 to 3.85), 1.62 (1.36 to 1.93) and 1.20 (1.10 to 1.30); fine motor, 1.93 (1.34 to 2.78), 1.55 (1.35 to 1.77) and 1.08 (1.01 to 1.15); problem solving, 1.80 (1.22 to 2.68), 1.36 (1.19 to 1.56) and 1.07 (1.00 to 1.14) and personal-social, 2.09 (1.29 to 3.40), 1.32 (1.07 to 1.63) and 1.00 (0.91 to 1.11). CONCLUSION: Moderate preterm, late preterm and early term births were associated with developmental impairment at age 3 years compared with full-term births, with increasing prematurity. Careful follow-up of non-full-term children by paediatricians and other healthcare providers is necessary for early detection of neurodevelopmental impairment and implementation of available intervention.

Effects of adenoid hypertrophy on nasopharyngeal airway ventilation: A computational fluid dynamics study.

OBJECTIVES: Adenoid hypertrophy causes impaired nasopharyngeal airways (NA) ventilation. However, it is difficult to evaluate the ventilatory conditions of NA. Therefore, this study aimed to analyze the nasopharyngeal airway resistance (NARES) based on computational fluid dynamics simulations and the nasopharyngeal airway depth (NAD) and adenoid hypertrophy grade measured on cephalometric cone-beam computed tomography images and determine the relationship between NAD and grade and NARES to ultimately assess using cephalometric measurements whether NA has airway obstruction defects. METHODS: Cephalogram images were generated from cone-beam computed tomography data of 102 children (41 boys; mean age: 9.14 ± 1.43 years) who received orthodontic examinations at an orthodontic clinic from September 2012 to March 2023, and NAD and adenoid grade and NARES values were measured based on computational fluid dynamics analyses using a 3D NA model. Nonlinear regression analyses were used to evaluate the relationship between NARES and NAD and correlation coefficients to evaluate the relationship between grade and NARES. RESULTS: NARES was inversely proportional to the cube of NAD (R2 = 0.786, P < 0.001), indicating a significant relationship between these variables. The resistance NARES increased substantially when the distance NAD was less than 5 mm. However, adenoid Grade 4 (75 % hypertrophy) was widely distributed. CONCLUSIONS: These study findings demonstrate that the ventilatory conditions of NA can be determined based on a simple evaluation of cephalogram images. An NAD of less than 5 mm on cephalometric images results in NA obstruction with substantially increased airflow resistance.

Association between gestational weight gain and risk of overweight at 3 years old: The Japan Environment and Children's Study.

BACKGROUND: It is unclear if gestational weight gain (GWG) increases the risk of children with overweight. OBJECTIVES: We examined the association between GWG and the risk of overweight in 3-year-old children in the Japanese nationwide birth cohort study. METHODS: Among 64 336 singleton births, we calculated the risk ratios (RRs) and 95% confidence intervals (95% CIs) of the association between GWG categories and children with overweight, following an adjustment of the confounding variables. RESULTS: GWG was positively associated with the risk of overweight among 3-year-old children. The multivariable RR (95% CI) was 1.21 (1.17-1.25) per 5 kg increase of the GWG. The multivariable RR (95% CI) for excessive GWG was 1.20 (1.12-1.28) and 1.27 (1.16-1.39) based on the modified Japanese and IOM criteria, respectively, compared to adequate GWG. The multivariable RR (95% CI) of overweight with children for inadequate versus adequate GWG was 0.83 (0.78-0.88) and 0.84 (0.79-0.89) based on the modified Japanese and IOM criteria, respectively. CONCLUSIONS: GWG was positively associated with a high risk of overweight at 3 years of age. The risk of offspring overweight was 20%-27% higher and 16%-17% lower with excessive GWG and inadequate GWG, respectively, compared to adequate GWG, based on the aforementioned criteria.